Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY 11209, USA.
Department of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Health Sciences University, New York, NY 11203, USA.
Int J Mol Sci. 2024 Aug 23;25(17):9155. doi: 10.3390/ijms25179155.
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are widely used for disease modeling and pharmacological screening. However, their application has mainly focused on inherited cardiopathies affecting ventricular cardiomyocytes, leading to extensive knowledge on generating ventricular-like hiPSC-CMs. Electronic pacemakers, despite their utility, have significant disadvantages, including lack of hormonal responsiveness, infection risk, limited battery life, and inability to adapt to changes in heart size. Therefore, developing an in vitro multiscale model of the human sinoatrial node (SAN) pacemaker using hiPSC-CM and SAN-like cardiomyocyte differentiation protocols is essential. This would enhance the understanding of SAN-related pathologies and support targeted therapies. Generating SAN-like cardiomyocytes offers the potential for biological pacemakers and specialized conduction tissues, promising significant benefits for patients with conduction system defects. This review focuses on arrythmias related to pacemaker dysfunction, examining protocols' advantages and drawbacks for generating SAN-like cardiomyocytes from hESCs/hiPSCs, and discussing therapeutic approaches involving their engraftment in animal models.
人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）广泛用于疾病建模和药物筛选。然而，它们的应用主要集中在影响心室心肌细胞的遗传性心脏病上，导致广泛的知识生成心室样 hiPSC-CMs。电子起搏器尽管具有实用性，但存在显著的缺点，包括缺乏激素反应性、感染风险、电池寿命有限以及无法适应心脏大小的变化。因此，使用 hiPSC-CM 和 SAN 样心肌细胞分化方案开发人类窦房结（SAN）起搏器的体外多尺度模型至关重要。这将增强对 SAN 相关病理学的理解，并支持靶向治疗。生成 SAN 样心肌细胞为生物起搏器和专门的传导组织提供了可能性，有望为传导系统缺陷的患者带来重大益处。本综述重点关注与起搏器功能障碍相关的心律失常，检查从 hESC/hiPSC 生成 SAN 样心肌细胞的方案的优缺点，并讨论涉及将其移植到动物模型中的治疗方法。
